The prevalence of neutralizing antibodies against adeno‐associated virus capsids is reduced in young Japanese individuals

作者：Jun Mimuro, Hiroaki Mizukami, Midori Shima, Tadashi Matsushita, Masashi Taki, Shinji Muto, Satoshi Higasa, Michio Sakai, Tsukasa Ohmori, Seiji Madoiwa, Keiya Ozawa, Yoichi Sakata · 发表于：Journal of Medical Virology · 年份：2013 · DOI：10.1002/jmv.23818 · 被引用次数：73 · 研究领域：Virus-based gene therapy research、CAR-T cell therapy research、Viral Infectious Diseases and Gene Expression in Insects

Pre-existing antibodies against adeno-associated virus (AAV), caused by natural AAV infections, interfere with recombinant AAV vector-mediated gene transfer. We studied the prevalence of neutralizing antibodies against AAV serotypes 1, 2, 5, 8, and 9 in healthy subjects (n = 85) and hemophilia patients (n = 59) in a Japanese population. For healthy subjects, the prevalence of neutralizing antibodies against AAV serotypes 1, 2, 5, 8, and 9 was 36.5%, 35.3%, 37.6%, 32.9%, and 36.5%, respectively, while that in hemophilia patients was 39.7%, 28.8%, 35.6%, 32.9%, and 27.4%, respectively. There was no difference in the prevalence of neutralizing antibody against each AAV serotype between the healthy subjects and the hemophilia patients. The prevalence of neutralizing antibodies against all AAV serotypes increased with age in both healthy subjects and hemophilia patients. High titers of neutralizing antibodies against AAV2 (≥1:224) and AAV8 (≥1:224) were more evident in older individuals (≥42 years old). Approximately 50% of all screened individuals were seronegative for neutralizing antibodies against each AAV tested, while approximately 25% of individuals were seropositive for each AAV serotype tested. The prevalence of seronegativity for all AAV serotypes was 67.0% (healthy subjects, 68.6%; hemophilia patients, 65.0%) and 18.6% (healthy subjects, 20.5%; hemophilia patients, 15.7%) in young (<42 years old) and older subjects (≥42 years old), respectively. The findings from this s...